Neural Dynamics Research Group

Our Mission

The Neural Dynamics Research Group is dedicated to determining the causes
and stages in the progression of various neurological diseases that
occur at different periods in life. These include developmental disorders
of the nervous system, such as ASD, as well as age-dependent disorders of
later life (ALS, Parkinson’s disease, Alzheimer’s disease). We believe that
our current model systems approach, as well as additional methods under
development, will allow us to achieve these goals. We hope to use the
knowledge derived from these models to push for translational medical
approaches to preventing or halting neurological diseases before the
underlying pathological mechanisms of action have done irreparable harm to
the nervous system. Our ultimate goal is to prevent neurodegenerative
diseases across the lifespan.

History of the laboratory by Dr.
Chris Shaw

I started the
laboratory in Ophthalmology in 1988 upon moving from Dalhousie to UBC. At
that time the lab was called the 'Receptor Lab' due to the research focus on
the role of various neurotransmitter receptors in neuroplasticity of visual
cortex with a focus on the early critical period. The lab had just begun
moving from the characterization of receptors frozen tissue to studies
focusing on living tissue. Much of the early work of the laboratory was
devoted to justifying the new techniques and providing data that
the 'in vitro living slice' could be used to characterize receptors.
Once this was done, we shifted our focus to a series of studies of
functional regulation of such receptors in response to biological
stimulation. In turn, the studies of regulation led to studies of the
mechanisms underlying regulation, i.e. the activation of various protein
kinases and phosphatases, the ions controlling such activation, etc. By this
time, my students and I had begun to realize that the process of
receptor regulation was very dynamic: neural activity changes caused
receptor regulation, in turn altering neural activity and so on. This
realization had a profound impact on our thinking about plasticity processes
in the developing and adult nervous system. It also had implications for
understanding neurological disease. These thoughts led to the editing of
my first book, "Receptor Dynamics in the Nervous System' (1996). During this
period we had a secondary focus on the role of glutathione in the brain and
the possibility that glutathione could be a neurotransmitter. These studies
culminated with the second book, "Glutathione in the Nervous System" (1998).

The next major
stage of laboratory development came when we began to collaborate with
various clinical researchers on ALS. Initially, these were simple receptor
assays on frozen material but the studies gradually expanded to examine
protein kinase and phosphatase activities as well. To our surprise, we found
that molecules affected by disease were the same as those involved in
neuroplastic modifications of neurons. This observation led to the notion
that plasticity and pathology are closely related mechanistically via a
continuum of events. These observations were the basis for a series of
review articles dealing with long-term potentiation, epilepsy, and
pathology. Ultimately, these articles formed the basis for the third edited
volume (with co-editor, Jill McEachern), "Toward a Theory of
Neuroplasticity" (2000).

Continuing with
our studies of degenerative diseases of the nervous system, especially ALS,
I became aware of an odd neurological disorder on the island
of Guam. This disease,
ALS-parkinsonism dementia complex (ALS-PDC) showed a number of
remarkable features that had led early investigators, notably Dr. LT
Kurland, to describe it as a neurological Rosetta Stone. Key features were
its incredibly high incidence, the incidence at earlier ages than seen
outside of Guam, and often grouping of
clinical and pathological features of ALS, parkinsonism, and Alzheimer's
disease. The strongest epidemiological link was to the consumption of the
seed of the cycad plant that contained
a neurotoxin. Surprisingly, no one had previously developed an animal model
of ALS-PDC in order to test this hypothesis. Our immediate goal became
that of developing such a model system of the disease in order to assess the
causal stages of neuronal degeneration. To do so, the lab had to shift focus
on a number of fronts. First, we changed from a predominant focus on
receptor assays to the study of a number of crucial molecules involved in
neurodegeneration. Next, we began to learn how to conduct behavioral
assessments of function in mice. At about this time the laboratory moved
from its previous 'home' in the Department of Anatomy (UBC campus) to its
current location at the Research Pavilion, VGH. At the same time, our
official name changed to the Neural Dynamics Research Group, reflecting a
general change in our outlook and focus on neurological diseases and
plasticity.

These efforts in
developing a mouse model of ALS-PDC have shown spectacular success and have
rewarded us with what we believe are crucial insights into the role of
environmental toxins as key factors in neurological disease, and some
important molecular events that lead to neural cell death. The skills the
lab has acquired along the way in various other projects are all utilized to
further probe the model. This model with its potential to provide a detailed
understanding of the causes and progression of neurodegeneration has become
the lab's sole focus and main effort. In consequence of this model and its
successful development, our grant funding has increased significantly, and
with this additional funding have come new faces and outlooks (See current
projects under Research link).

Most
recently we have broadened our focus to look at other neurotoxins that may
contribute to neurological disorders in different phases of life.One of the toxins we are now examining both
in vitro and
in vivo is aluminum which is well known for its neurotoxic
potential.Our current studies are
looking at both dietary and injection routes of delivery of aluminum at
different ages.The goal is to model
both the features of late onset neurological disorders such as those we have
previously worked on (ALS, PD, AD), but also to examine the impacts of
aluminum in earlier life.In regard
to the latter, we are attempting to model aspects of autism spectrum
disorder (ASD), the latter which correlates with a high degree of
significance in humans with the number of aluminum-adjuvanted vaccines
administered in early life.